Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 30, 2015
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: (-)-α-Kainic Acid (Ohshima), Serpentine (Scheidt), (-)-Galanthamine (Jia), (+)-Trigolutes B (Gong), Sarain A (Yokoshima/Fukuyama), DZ-2384 (Harran)

(-)-α-Kainic Acid (3) is widely used in neuropharmacological studies. En route to 3, Takashi Ohshima of Kyushu University found (Chem. Eur. J. 2015, 21, 3937. DOI: 10.1002/chem.201406557) that the intramolecular ene cyclization of 1 delivered 2 with high diastereocontrol.

Karl A. Scheidt of Northwestern University set (Angew. Chem. Int. Ed. 2015, 54, 6900. DOI: 10.1002/anie.201502011) the absolute configuration of 5 and so of Serpentine (6) by the organocatalyzed cyclization of 4. This is the first total synthesis of that alkaloid.

Yanxing Jia of Peking University prepared (Angew. Chem. Int. Ed. 2015, 54, 6255. DOI: 10.1002/anie.201411338) the benzofuran 8 by the Pd-mediated cyclization of the alkyne 7. An organocatalyzed intermolecular Michael addition set the absolute configuration of (-)-Galanthamine (9).

Liu-Zhu Gong of the University of Science and Technology of China assembled (Chem. Eur. J. 2015, 21, 8389. DOI: 10.1002/chem.201500349) (+)-Trigolutes B (13) by the organocatalyzed addition of 10 to 11 to give 12. Barry M. Trost of Stanford University employed (Chem. Sci. 2015, 6, 349. DOI: 10.1039/C4SC01826E) a similar strategy in a synthesis of (-)-Perophoramidine (not illustrated).

Satoshi Yokoshima and Tohru Fukuyama of Nagoya University showed (Angew. Chem. Int. Ed. 2015, 54, 7367. DOI: 10.1002/anie.201501633) that on deprotection, 14 was converted to an eight-membered cyclic nitrone, that further cyclized to 15. This set the stage for the synthesis of Sarain A (16).

Patrick G. Harran of UCLA has extensively studied the complex alkaloid (-)-Diazonamide A (not illustrated). Structural simplification and optimization of the anti-mitotic activity led to the macrolactam DZ-2384 (18). It is exciting that 18 could be prepared (Angew. Chem. Int. Ed. 2015, 54, 4818. DOI: 10.1002/anie.201411663) on a multi-gram scale by selective electrochemical oxidation of the much simpler precursor 17.

D. F. Taber, Org. Chem. Highlights 2015, November 30.